Effect of salvia miltiorrhiza on gentamicin-induced activity of NF-κB in the cochlea of guinea pig

【Objectives】 To investigate the effect of salvia miltiorrhiza (SM) on gentamicin(GM)-induced activity of nuclear factor-kappa B (NF-κB) in the cochlea of guinea pig, and to explore the protective role and molecular mechanism of SM on GM-induced totoxicity. 【Methods】 Guinea pigs were randomly assigned to four groups: normal control,GM alone,GM plus SM and SM alone. SP method of immunohistochemistry was applied to detect the expression of NF-κB P65 and NF-κB P50,combined with auditory brainstem response (ABR) measurement to observe the changes of auditory threshold.【Results】 Compared with normal controls, ABR thresholds were elevated significantly in GM alone group.Co-treatment with SM resulted in significant reduction of ABR thresholds as compared with GM alone. Immunoreactivity for NF-κB P65 was only observed in the spiral ligament in the cochlea of normal control. Localization of NF-κB P65 in the cochlea of guinea pigs from other three groups was similar to that of con-trol.There were no obvious difference among them. Immunoreactivity for NF-κB P50 was detected in the spiral ligament, stria vascularis, spiral ganglion, nerve fiber, limbus laminae spiralis osseae and spiral organ in the cochlea of normal control.Localization of NF-κB P50 in the cochlea of guinea pigs from GM and GM+SM groups was similar to that of control.But the activity of NF-κB P50 in spiral ligament and stria vascularis in GM group was greater than that in normal control.Whereas the activity of NF-κB P50 in GM+SM group was lower than that in GM group. NFκB P50 immunostaining was observed in cytoplasm but not in nuclei of the outer hair cells in both normal control and SM alone.After treatment with GM,immunostaining with NF-κB P50 was present in nuclei of outer hair cells of GM.However, concomitant injection of SM was no nuclear immunostaining for P50.There was no positive staining of NF-κB P50 in the sections of negative control.Linear correlation test was applied to analyze the average gray of NFκB P50 and ABR threshold,and negative correlation was gained.【Conclusion】 Expression of NF-κB P65 and NFκB P50 was observed in the cochlea in normal guinea pigs. After treatment with GM,NF-κB was activated and hearing was injured.SM could effectively attenuate GM ototoxicity by inhibiting the activity of NF-κB induced by GM, this might be one of the molecular mechanism by which SM could protect against GM ototoxicity.